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Genetic counseling: Bloom Syndrome-1
Bloom Syndrome Genetics *Mutation of BLM gene at chromosome 15q26.1 *Common Ashkenazi Jewish mutation- blmASH (2281del6ins7) *Abnormalities in DNA repair and chromosomal structure **increased chromosome breakage **increased rate of homologous chromosome exchange **formation of quadriradial (QR) configuration in mitosis **increased rate of sister chromatid exchanges (SCEs) **unique to Bloom Syndrome Incidence *Ashkenazi Jewish population *Carrier frequency 1 in 107 *Incidence 1/160,000 *Very rare in Non-Ashkenazi Jewish populations Diagnosis *Characteristic clinical features *Demonstration of symmetric QR interchange configuration and increased number of SCEs *Demonstration of mutations in both BLM genes Clinical Features *Predominant features **Small body size ***Mean birth weight 1906 g in males and 1810 g in females ***Mean adult height 147.5 cm in males and 138.6 cm in females **Predisposition to cancer- of all cell types and at all sites *Additional features which may or may not be present **Characteristic facies- keel-shaped face, dolicocephaly, narrow cranium, malar hypoplasia, nasal prominence, small mandible, and prominent ears. **Hypersensitivity to sunlight- formation of sun-sensitive erythema (telangiectasia) on face and possible hands/forearms **Areas of hyper- and hypo- pigmented skin- café-au-lait spots **High-pitched and somewhat squeaky voice **Vomiting and diarrhea during infancy **Diabetes mellitus- generally with onset in the second or third decade **Failure of spermatogenesis in males **Early cessation of menstruation and reduced fertility in females **General immunodeficiency- often associated with ottitis media and pneumonia **Slightly increased incidence of minor anatomic anomalies including anomalous digits, pilonidal dimples, wedges of altered color of the irides, and obstructing anomalies of the urethra **Restricted intellectual ability- generally average to low-average intelligence but can be more severe Natural History *Intrauterine Growth Deficiency *full-term infants tend to have low birth weight *Onset of facial skin lesion usually in first or second summer, can be later *Cancer predisposition throughout life- always higher than age-associated risk *Mean age of cancer diagnosis 24.7 (range of 2 to 48 years) *Mean age of death is 23.6 years (range from <1 to 49) *Cancer is the most common cause of death Inheritance *Autosomal Recessive Testing *Cytogenic analysis *Increased in number or chromatid gaps, breaks, and interchanges *Increase in the number of sister-chromatid exchanges (SCEs) *Can be performed on any cell which can be brought into mitosis *Molecular Genetic Analysis *Clinical testing for common Ashkenazi Jewish mutation- blmASH *98% detection for Ashkenazi Jewish Bloom syndrome patients *Research testing - full gene screening for affected individuals *Memorial Sloan-Kettering Cancer Center *Prenatal diagnosis *Sister chromatid exchange assay via amnio or CVS *Amnio or CVS for known familial mutation Management & Treatment *No treatment for growth deficiency *Protection from the sun decreases severity of skin lesion *Careful monitoring for cancer *Cancer treatment must consider hypersensitivity to DNA-damaging chemicals Differential Diagnosis *Other syndromes associated with sun sensitivity and telangiectasias: *Erythropoietic protoporphyria *Rothmund-Thomson syndrome *Cockayne syndomre *Hereditary hemorrhagic telangiectasia *Ataxia telangiectasia Psychosocial Issues *Physical appearance may affect self-image, confidence *Reduced life expectancy *High probability of malignancy Patient Resources *Bloom's Syndrome Registry :NY Blood Center :310 East 67th Street :New York, NY 10021 :Phone: (212) 570-3075 *National Foundation for Jewish Genetic Diseases, Inc. (NFJGD) :250 Park Ave, Suite 1000 :New York, NY 10177 :Phone: (212) 371-1030 :Web *Xeroderma Pigmentosum Society, Inc. :Box 4759 :Poughkeepsie, NY 12602 :Phone: (518) 851-2612 :Web :E-mail: xps@xps.org Case Specifics *See attached References *Byarlay, J. and Goldsmith, L. (1997) Other Genetic Disorders of the Skin. In Rimoin, D, Connor, J, and Pueritz, R ed. Principles and Practice of Medical Genetics. Churchill Livingstone: New York. 1309-1310. *German, J. and Ellis, N. (2001). Bloom Syndrome. In Scriver, C., Beaudet, A., Sly, W., and Velle, D. ed. Metabolic and Molecular Bases of Inherited Disease. McGraw Hill: New York. 733-751. *Goodman, R. (1979) Genetic Disorders among the Jewish People. Johns Hopkins University Press: Baltimore. 73-79. Notes The information in this outline was last updated in March 2003. Material obtained under GFDL Licence from http://en.wikibooks.org/wiki/Handbook_of_Genetic_Counseling